---
title: "Impact of Adjuvant Immune Checkpoint Inhibitors on HRQoL in Renal Cell Carcinoma: Qualitative RAMP"
id: "plos-one-10-health-related-quality-of-life-with-adjuvant-immune-checkpoint-inhibition-in"
canonical_url: "https://medichelpline.com/clinical-feed/plos-one-10-health-related-quality-of-life-with-adjuvant-immune-checkpoint-inhibition-in"
content_type: "clinical_feed_article"
specialty: "Oncology"
source_name: "PLOS ONE (Medicine)"
source_url: "https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0358789"
published_at: "2026-09-21T14:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Impact of Adjuvant Immune Checkpoint Inhibitors on HRQoL in Renal Cell Carcinoma: Qualitative RAMP
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/plos-one-10-health-related-quality-of-life-with-adjuvant-immune-checkpoint-inhibition-in
- **Specialty:** [Oncology](https://medichelpline.com/clinical-feed/oncology.md)
- **Primary Source:** PLOS ONE (Medicine)
- **Source URL:** [Original Journal Publication](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0358789)
- **Published At:** 2026-09-21T14:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- This qualitative sub-study within the phase III RAMPART trial interviewed 23 UK participants who received adjuvant **immune checkpoint inhibitors (ICIs)** after nephrectomy for renal cell carcinoma to explore impacts on **health-related quality of life (HRQoL)**. - Participants were purposively sampled to represent trial arm (durvalumab alone or durvalumab plus tremelimumab), toxicity experience, treatment tolerance, and recurrence status; median age was 57, all identified as White, 12 were in the combination arm and 11 in the monotherapy arm. - All interviewees reported at least one adverse event (AE); 52% experienced grade ≥3 toxicity, median AE duration was 29 days (IQR 8–118), and 65% had unresolved AEs at data cut-off. Nine participants received corticosteroids; one required further immunosuppression for immune-mediated myasthenia gravis. - Two central themes emerged: “Living in a Changed Body and Mind” and “It Depends on Your Life: How Context Shapes the Impact of immune-related adverse events (irAEs).” Participants emphasized **duration and chronicity** of irAEs over peak severity when describing HRQoL impact. - Persistent symptoms (fatigue described as “bone deep,” arthralgia, diarrhoea), cognitive changes, and emotional strain disrupted daily functioning, employment, and social roles; supportive relationships and structured follow-up mitigated burden. - Participants often adjusted activities to accommodate persistent low-grade toxicities; the unpredictable or fluctuating nature of symptoms increased uncertainty and psychosocial strain. - Findings highlight that standard PROMs used in oncology trials (e.g., QLQ-C30, EQ-5D, FACT) may miss ICI-specific or chronic toxicities; trial reporting should include toxicity grade, duration, and resolution. - The study recommends development of ICI-specific HRQoL tools, clearer survivorship care pathways for chronic irAEs, and improved trial assessment schedules to capture late-onset or persistent toxicities. - Limitations noted include lack of ethnic diversity (all participants identified as White) and under-representation of people aged ≥75; transcripts were not returned to participants for member checking. - These qualitative insights aim to inform clinical decision-making, trial design, survivorship care, and future research around adjuvant ICIs in RCC.
## Clinical Analysis & Structured Key Points
Health-related quality of life with adjuvant immune checkpoint inhibition in renal cell carcinoma: A qualitative study of UK participants in the phase III RAMPART trial | PLOS One Browse Subject Areas ? Click through the PLOS taxonomy to find articles in your field. For more information about PLOS Subject Areas, click here . Article Authors Metrics Comments Media Coverage Reader Comments Figures Figures Abstract Introduction RAMPART is an international phase III trial evaluating adjuvant immune checkpoint inhibitors (ICIs) after nephrectomy for renal cell carcinoma. ICIs have a distinct toxicity profile that can significantly impact health-related quality of life (HRQoL); however existing HRQoL questionnaires were developed in a pre-ICI era and may not fully capture the patient experience. To address this, we embedded a qualitative interview sub-study within RAMPART among UK participants to explore the impact of ICIs on HRQoL in depth. Methods Eligible participants were enrolled in RAMPART at UK sites and randomised to Arm B (durvalumab q4w for 1 year) or C (durvalumab q4w for 1 year plus tremelimumab at day 1 and week 4). Participants were purposively selected to ensure representation across baseline characteristics, treatment tolerance, toxicity development, and recurrence status. Interviews were conducted online, via telephone and in person, with transcripts analysed using the framework method. Results Of 220 eligible participants, 71 were invited; with recruitment closing early due to a high response rate. 37 expressed interest, and 23 were interviewed. Two themes were generated based on participant insights: Living in a Changed Body and Mind and It Depends on Your Life: How Context Shapes the Impact of Immune Related Adverse Events (irAEs) . The findings suggest that participants often placed greater importance on the duration and chronicity of irAEs than their severity when describing impacts on HRQoL. Persistent toxicities, including fatigue, arthralgia, and diarrhoea, disrupted daily functioning, while cognitive changes and emotional strain were common. Employment, financial security, and caregiving responsibilities influenced the impact of irAEs, whereas supportive relationships and structured follow-up mitigated their burden. Conclusions Chronic irAEs can negatively affect HRQoL, mental health, and the ability to work. Clinical trials evaluating ICIs should report toxicity grade, duration, and resolution to better inform patient decision-making. Development of ICI-specific HRQoL tools that capture the impact of persistent irAEs is needed, alongside clear care pathways for management of chronic irAEs. Citation: Merrick S, South A, Frangou E, Rush HL, Patel G, Thompson J, et al. (2026) Health-related quality of life with adjuvant immune checkpoint inhibition in renal cell carcinoma: A qualitative study of UK participants in the phase III RAMPART trial. PLoS One 21(9): e0358789. https://doi.org/10.1371/journal.pone.0358789 Editor: Alireza Shoari, Mayo Clinic Cancer Center, UNITED STATES OF AMERICA Received: July 16, 2026; Accepted: September 5, 2026; Published: September 21, 2026 Copyright: © 2026 Merrick et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability: Anonymised interview transcripts cannot be made publicly available due to the risk of participant re-identification. Participants consented to controlled sharing of anonymised transcripts with other researchers for future research. Requests for access should be directed to mrcctu.rampart@ucl.ac.uk and will be considered in accordance with participant consent, ethical approvals, and our institutional data sharing policy: https://www.innovative-ctu.ucl.ac.uk/our-research/other-research-policy/data-sharing/ . Funding: This study was funded by Kidney Cancer UK. RAMPART is sponsored by UCL and funded by AstraZeneca. Sophie Merrick is supported by a Cancer Research UK Fellowship (grant number RCCCTF-Nov21\100002). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: This qualitative study was funded by Kidney Cancer UK. RAMPART is sponsored by UCL and funded by AstraZeneca. JL reports honoraria (Eisai, Novartis, Incyte, Merck, touchIME, touchEXPERTS, Pfizer, Roche, BMS, iOnctura, Dynavax, CRUK, GSK); consultancy (iOnctura, Apple Tree, Merck, BMS, Eisai, GSK, Incyte, Pfizer, Novartis, MSD, Iovance, Boston Biomedical, YKT Global, Immunocore); speaker fees (Pierre Fabre, BMS, Ipsen, Roche, EUSA Pharma, Novartis, Aptitude, AstraZeneca, GSK, Eisai, Calithera, Ultimovacs, Seagen, Merck, eCancer, Pfizer, MSD, Ervaxx); institutional research support (BMS, MSD, Novartis, Pfizer, Achilles Therapeutics, Roche, Nektar Therapeutics, Covance, Immunocore, Pharmacyclics, Aveo); grants (Achilles, BMS, MSD, Nektar, Novartis, Pfizer, Roche, Immunocore, Aveo, Pharmacyclics, NIHR Royal Marsden-Institute of Cancer Research Biomedical Research Centre). TP reports honoraria (AstraZeneca, BMS, Exelixis, Incyte, Ipsen, Merck/MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai, Roche, Mashup, Gilead); grant/funding to institution (AstraZeneca, Roche, BMS, Exelixis, Ipsen, Merck/MSD, Novartis, Pfizer, Seattle Genetics, Merck Serono, Astellas, Johnson & Johnson, Eisai). All other authors declare no competing interests. This does not alter our adherence to PLOS ONE policies on sharing data and materials. Introduction Locoregional renal cell carcinoma (RCC) is primarily managed with radical or partial nephrectomy [ 1 ]. However, patients at intermediate or high risk of recurrence face substantial relapse rates, prompting investigation into adjuvant systemic therapies. Immune checkpoint inhibitors (ICIs) have therefore been evaluated in this setting with mixed results. Pembrolizumab has demonstrated improvements in disease free survival (DFS) and overall survival (OS) in patients with resected clear cell RCC [ 2 , 3 ]. Several other perioperative or adjuvant trials have not met their primary endpoints [ 4 – 7 ]. Within this evolving landscape, the RAMPART trial, is evaluating adjuvant durvalumab (anti–programmed death-ligand 1) alone or in combination with tremelimumab (anti–cytotoxic T-lymphocyte–associated protein 4) in patients at intermediate or high risk of relapse. At the primary analysis, durvalumab plus tremelimumab significantly improved DFS compared with active monitoring, while durvalumab monotherapy did not [ 8 ]. While DFS and OS are paramount, adjuvant therapy must also be assessed for its impact on health-related quality of life (HRQoL) [ 9 , 10 ]. ICIs present specific challenges: immune-related adverse events (irAEs) can arise unpredictably, affect any organ system, and persist long after treatment cessation [ 11 – 17 ]. Some irAEs necessitate prolonged immunosuppression or lifelong hormone replacement, introducing chronic health burdens for patients who may otherwise be cured [ 11 , 13 , 15 ]. Understanding how acute and chronic irAEs impact HRQoL is critical to informed decision-making. Regulatory agencies and Health Technology Assessment bodies increasingly require HRQoL outcomes to inform benefit–risk assessment and policy decisions [ 18 ]. HRQoL in oncology trials is typically evaluated using patient-reported outcome measures (PROMs). Common instruments include the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), the EuroQol 5-Dimension (EQ-5D), and the Functional Assessment of Cancer Therapy (FACT) questionnaires [ 19 , 20 ]. However, these instruments were developed in a pre-immunotherapy era and lack sensitivity to irAEs such as rash, arthralgia, and endocrinopathies as well as prolonged toxicities and the burden of ongoing immunosuppression. The HRQoL impact of many of these chronic or fluctuating effects is still poorly understood. Multiple systematic reviews have highlighted that existing PROMs lack adequate content validity for patients receiving ICIs, raising concerns that they may underestimate treatment burden and fail to capture survivorship issues unique to ICIs [ 19 , 21 , 22 ]. Trial assessment schedules may also fail to identify late onset or persistent irAEs. To address these limitations in understanding the impact of ICIs on HRQoL, we conducted a qualitative sub-study within RAMPART (NCT03288532) to explore patient experiences beyond the scope of standardised questionnaires. To our knowledge, this is the first qualitative study to examine the impact of adjuvant ICI on HRQoL in RCC. Findings inform clinical decision‑making, trial design, survivorship care and future research. We present the results alongside recommendations co‑developed with patients and multidisciplinary experts. Methods Study design and research team This qualitative interview study was embedded within the RAMPART trial and conducted within a critical realist paradigm [ 23 ]. This approach recognised participants’ accounts as reflecting real experiences of treatment-related toxicity while also acknowledging that these experiences were shaped by individual contexts. Consequently, analysis considered not only the direct effects of irAEs but also how personal circumstances influenced their impact on HRQoL. Consistent with critical realism, interpretation was understood to be influenced by researchers’ backgrounds and perspectives; therefore, analysis was undertaken collaboratively by clinical and non-clinical researchers to support reflexive interpretation of the data. The research team comprised three oncology clinicians (SM, HLR, GP) and two non-clinical researchers (AS, JT). SM, a female clinical research fellow, conducted all interviews. SM, HLR, AS, and JT had prior qualitative research experience; GP contributed clinical expertise. A patient and public involvement (PPI) representative with lived experience of RCC contributed to the study design, participant materials and interview guide, which was piloted with a patient. This study is reported in accordance with the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist [ 24 ]. The interview guide and COREQ checklist are provided in the Supporting Information ( S1 and S2 File ). Participants and recruitment Eligible participants were enrolled in RAMPART at UK sites, received ICI in Arm B (durvalumab 1500 mg every 4 weeks for 1 year) or Arm C (durvalumab 1500 mg every 4 weeks for 1 year plus tremelimumab 75 mg at day 1 and week 4), and had completed ≥2 QLQ-C30 questionnaires (used for eligibility only; questionnaire data not included in this analysis). Participants were identified centrally and invited by post through research nurses at participating sites. Sites were approached in waves as they activated the sub-study, with later waves targeting underrepresented demographics. Sampling was purposive, aiming for diversity in age, gender, ethnicity, trial arm and range of toxicity experience (see S3 File for purposive sampling framework, including target and achieved recruitment across categories). Recruitment ended once sampling matrix categories were filled or deemed unfillable. Sampling targets were achieved across all predefined characteristics except ethnicity and age ≥ 75 years. Despite targeted recruitment efforts, no participants from Black or Asian ethnic groups expressed interest in participation, and only two participants aged ≥75 years were recruited (target n = 3). No participants were known to SM (the interviewer) or treated at hospitals where SM worked, and all were aware that SM was an oncology clinician and researcher. Sample size We did not prespecify an exact number of participants. A purposive sampling matrix with minimum targets for age, gender, ethnicity, trial arm and toxicity experience guided recruitment (see S3 File ). Sample size was informed by the principle of Information Power, considering the focused study aim, the specificity of the sample, the richness of interview data and use of both within- and cross-case analysis [ 25 ]. Recruitment ceased once sampling matrix categories were filled or deemed unfillable and the multidisciplinary research team agreed that the final sample provided sufficient information power to address the study aims [ 25 ]. Ethical approval and consent to participate Ethical approval was obtained from the London Riverside Research Ethics Committee (17/LO/1875; Substantial Amendment 27, IRAS ID: 219487). All participants provided written informed consent prior to participation. Participants consented to the use of anonymised quotations in study outputs. The study was conducted in accordance with the Declaration of Helsinki and UK General Data Protection Regulation requirements. Participants were informed that confidentiality would be maintained unless there were concerns regarding risk of harm to themselves or others. A safeguarding procedure was in place whereby any disclosures of significant psychological distress, suicidal ideation, or safety concerns were assessed by the interviewer (SM), a medically qualified oncology clinician, and escalated to appropriate healthcare professionals if required. Participants were also signposted to relevant support services where appropriate. Although some participants described previous experiences of severe depression or suicidal ideation, no active safeguarding concerns requiring escalation were identified during the study. Data collection Baseline characteristics, treatment details, adverse event (AE) data, and concomitant medication were collected prospectively within the RAMPART trial. Semi-structured interviews were conducted via Microsoft Teams, telephone, or in person, with only the interviewer and participant present. Interviews explored experiences of ICI treatment, irAEs, and perceived impact on HRQoL. Participants were presented with vignettes illustrating severe or chronic irAEs (see S2 File ). The interview guide was used flexibly, with participants encouraged to discuss their experiences in their own words. Open-ended questioning and probing were used to explore issues raised by participants in greater depth. Interviews were recorded, transcribed, anonymised, and accompanied by field notes. Participants received a £25 voucher. Data analysis Transcripts were analysed using the framework method, which involves familiarisation, framework development, indexing, charting, and interpretation [ 26 , 27 ]. These stages were applied iteratively, and an overview is shown in Fig 1 A thematic framework was developed by SM and AS, informed by HRQoL domains and concepts from the data, and refined after initial coding (see S4 File ). Transcripts were indexed using this framework, and a matrix of summaries for each domain and case (interviewee) was constructed to facilitate cross-case analysis. Selected excerpts were reviewed in data clinics by AS, HLR, JT, and GP. NVivo14 supported data management [ 28 ]. Download: PNG larger image TIFF original image Fig 1. Overview of the framework analysis process. The arrow between framework development and charting indicates that analysis was iterative, with the framework refined as coding and charting progressed. https://doi.org/10.1371/journal.pone.0358789.g001 Transcripts were not returned to participants for member checking. Recommendation development Following analysis, preliminary recommendations were drafted based on study findings. We held a PPI workshop with 10 interview participants, where we presented preliminary findings, got their reactions to them, and then asked them to review and refine the draft recommendations. Participants suggested amendments and additions to ensure recommendations reflected patient priorities. The revised recommendations were then reviewed by a multidisciplinary expert panel of clinicians, trialists and methodologists (SM, GP, DG, AM, AS) to confirm clinical relevance and feasibility. Results Participant recruitment and characteristics Between 1 st September 2024 and 31 st March 2025, 71 of 220 eligible RAMPART participants were invited to join the qualitative sub-study. Recruitment closed early due to a high response rate. 37 participants expressed interest and 23 were purposively selected according to the predefined sampling framework ( S3 File ; Fig 2 ). Download: PNG larger image TIFF original image Fig 2. Participant selection. https://doi.org/10.1371/journal.pone.0358789.g002 Median age was 57 years (range 41–76); 14 participants were male and 9 female. All identified as White. 12 were in Arm C and 11 in Arm B; four had experienced recurrence. Characteristics are presented in Table 1 . Download: PNG larger image TIFF original image Table 1. Participant characteristics. https://doi.org/10.1371/journal.pone.0358789.t001 Treatment completion and toxicity Treatment completion and toxicity data were obtained from the RAMPART dataset. All participants had completed trial treatment by the time of interview. 10 received all planned treatment; 13 (57%) discontinued early (eight in Arm C; five in Arm B) due to toxicity (n = 10), COVID-19 disruption (n = 2), or patient choice (n = 1). All participants reported at least one AE, 12 (52%) had grade ≥3 toxicity ( Table 1 ). Common grade ≥3 AEs included laboratory abnormalities (9/23, 39%), gastrointestinal (5/23, 22%), and endocrine (2/23, 9%). Median AE duration was 29 days (IQR 8–118), and 15 participants (65%) had unresolved AEs at data cut-off. Nine participants (39%) received corticosteroids; one required additional immunosuppressive therapy for immune-mediated myasthenia gravis. Full AE frequencies, grading and duration are provided in the S5 and S6 File . Interview procedures 23 interviews were conducted between September 2024 and April 2025 (14 online, 7 telephone, 2 in person). Median time from treatment completion to interview was 33.4 months (range: 23.4–66.5). Median interview duration was 40 minutes (range 25–78). Interview findings Two themes were generated from the transcript analysis: ‘Living in a Changed Body and Mind’ and ‘It Depends on Your Life: How Context Shapes the Impact of irAEs’ . Each theme comprises several subthemes ( Fig 3 ). Quotes are anonymised using unique identifiers. Download: PNG larger image TIFF original image Fig 3. Overall thematic framework: how irAEs affect health-related quality of life. https://doi.org/10.1371/journal.pone.0358789.g003 Theme 1: Living in a changed body and mind Participants described a range of physical and psychological changes during and after ICI treatment. They also reflected on hypothetical scenarios, which were used to explore how the duration of irAEs, rather than their clinical severity, might influence HRQoL. Across both lived experience and scenario responses, duration emerged as the most important factor shaping impact. Subtheme 1.1 When it does not go away: the lingering impact of irAEs. For some, persistent symptoms long after treatment stopped created ongoing disruption and uncertainty. Even low-grade irAEs interfered with daily functioning and wellbeing. “The side effects that I've had to deal with have gone on some of them for a very long time. And it's not a case of they lessen - it's a case of you work out how you can work around them.” (P5) Fatigue was the most common and debilitating chronic symptom, often described as “bone deep” and unpredictable, with a cumulative toll on functioning. “It’s not just tiredness, it’s like your body just gives up. You can’t push through it.” (P7) Arthralgia also persisted for several participants, affecting mobility and comfort over extended periods. While some experienced intermittent discomfort, others described widespread, ongoing pain that interfered with daily activities. “It start
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